The Effectiveness and Safety of Nafamostat Mesylate in the Treatment of COVID-19: a Meta-Analysis.

Nafamostat mesylate, a synthetic serine protease inhibitor, has been shown to have antiviral activity against SARS-CoV-2 and anticoagulant properties that may be beneficial in the treatment of COVID-19. We conducted a meta-analysis to evaluate the effectiveness and safety of nafamostat mesylate for the treatment of COVID-19. PubMed, Embase, Cochrane Library, Scopus, Web of Science, medRxiv, and bioRxiv were searched up to July 2023 for studies comparing the outcomes of nafamostat mesylate treatment and no nafamostat mesylate treatment in patients with COVID-19. Mortality, disease progression, and adverse events were analyzed. Six studies involving 16,195 patients were included in the analysis. Meta-analysis revealed no significant difference in mortality (odds ratio [OR]: 0.88, 95% CI: 0.20-3.75, P = 0.86) or disease progression (OR: 2.76, 95% CI: 0.31-24.68, P = 0.36) between groups. However, nafamostat mesylate was associated with an increased risk of hyperkalemia (OR: 7.15, 95% CI: 2.66-19.24, P < 0.0001). Nafamostat mesylate did not improve mortality or morbidity in hospitalized patients with COVID-19. The risk of hyperkalemia is a serious concern that requires monitoring and preventive measures. Further research in different COVID-19 populations is required.

Efficacy and Safety of Direct Oral Anticoagulants Compared With Heparin for Preventing Thromboembolism in Hospitalized Patients With COVID-19: A Systematic Review and Meta-Analysis.

A high rate of thromboembolism and a high risk of death have been reported regarding hospitalized patients with coronavirus disease 2019 (COVID-19). Recently, we noticed that clinicians in some comparative studies used direct oral anticoagulants (DOACs) to prevent thromboembolism in patients with COVID-19. However, it is uncertain whether DOACs are better than recommended heparin for hospitalized patients with COVID-19. Therefore, a direct comparison of the prophylactic effects and safety between DOACs and heparin is needed. We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from 2019 to December 1, 2022. Randomized controlled trials or retrospective studies comparing the efficacy or safety of DOACs with that of heparin in preventing thromboembolism for hospitalized patients with COVID-19 were included. We assessed endpoints and publication bias using Stata 14.0. Five studies comprising 1360 hospitalized COVID-19 patients with mild to moderate cases were identified in the databases. Comparing the embolism incidence, we found that DOACs had a better effect than heparin, mainly low-molecular-weight heparin (LMWH), in preventing thromboembolism (risk ratio [RR] = 0.63, 95% confidence interval [CI] [0.43-0.91], P = 0.014). Considering safety, DOACs resulted in less bleeding than heparin during hospitalization (RR = 0.52, 95% CI [0.11-2.44], P = 0.411). Similar mortality was discovered in the 2 groups (RR = 0.94, 95% CI [0.59-1.51], P = 0.797). In noncritically hospitalized patients with COVID-19, DOACs are superior to heparin, even LMWH, in preventing thromboembolism. Compared with heparin, DOACs have a lower trend of bleeding and yield a similar mortality rate. Therefore, DOACs may be a better alternative for patients with mild to moderate COVID-19.

The Association between the Fibrosis-4 Index and COVID-19: A Systematic Review and Meta-Analysis.

OBJECTIVE: The prognosis value of fibrosis-4 score (FIB-4) in COVID-19 is controversial. Hence, we conducted a systematic review and meta-analysis to investigate the association between the FIB-4 index and COVID-19 disease progression. METHODS: We performed meta-analysis using the PubMed, Embase, and Cochrane databases. A fixed- or random-effects model was used for evaluating heterogeneity. RESULTS: Thirteen studies were included. The meta-analysis of unadjusted results showed that compared to lower FIB-4 index, patients with higher FIB-4 index had increased odds of mortality (OR=5.1, 95%CI 3.67-7.09; P<0.001), ICU admission (OR=2.32, 95%CI: 1.65-3.25, P<0.00001) and need for mechanical ventilator support (OR=3.51, 95%CI: 2.1-5.85, P<0.001). In addition, the meta-analysis of adjusted results showed patients with higher FIB-4 index was associated with increased risk of mortality (OR=3.01, 95%CI: 2.21-4.09, P<0.001) and need for mechanical ventilator support (OR=3.76, 95%CI: 2.08-6.82, P<0.001) compared to patients with lower FIB-4 index. CONCLUSIONS: This meta-analysis indicated that high FIB-4 index score was associated with the severity and mortality in COVID-19 infected patients.

Opioid usage and COVID-19 prognosis: A systematic review and meta-analysis.

The COVID-19 pandemic continues to have profound health, social, psychological, and economic ramifications. Infection by COVID-19 has been of concern in people who use opioids, as opioid use has been known to mediate immunosuppression and is associated with respiratory depression and end-organ damage. With differing modalities of opioid usage, the association between opioids and COVID-19 outcomes is not well understood. We performed a comprehensive systematic search of seven health science databases, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data, up to December 15, 2021. We identified a total of five related articles, which were included in this study. The meta-analysis showed that opioids have a significant association with ICU admission for COVID-19 patients (OR = 5.41, 95%CI: 1.85 to 15.79, P = 0.002). Use of opioids was also associated with higher mortality among patients with COVID-19 compared to non-users (OR = 2.74, 95%CI: 1.34 to 5.62, P = 0.034), while use of opioids was not significantly associated with need for mechanical ventilation (OR = 3.68, 95%CI: 0.85 to 15.90, P = 0.081). Furthermore, the adjusted analysis indicated that COVID-19 patients with a history of opioid use were more likely to be admitted to the ICU (OR = 3.57, 95%CI: 3.05 to 4.17, P<0.001) and have higher mortality rates (OR = 1.72, 95%CI: 1.09 to 2.72, P = 0.02), while there was no significant association with need for mechanical ventilation (OR = 2.09, 95%CI: 0.77 to 5.64, P = 0.146). Significant heterogeneity existed across the included studies. Patients using opioids with COVID-19 were at higher risk of ICU admission and mortality. Prospective studies are required to confirm these findings.

Intravenous vitamin C use and risk of severity and mortality in COVID-19: A systematic review and meta-analysis.

The administration of intravenous vitamin C (IV-VC) in treating patients with coronavirus disease 2019 (COVID-19) is still highly controversial. There have been no previous studies on the effect of IV-VC on the severity and mortality of COVID-19. Hence, we conducted a systematic review and meta-analysis to compare the disease severity and mortality in patients with COVID-19 who promptly received IV-VC treatment vs those who did not. We performed a comprehensive systematic search of seven health science databases, including PubMed, Embase, Cochrane Library, MEDLINE, Web of Science, China National Knowledge Infrastructure, and Wanfang Data, up to June 23, 2021. We identified a total of seven related articles, which were included in this study. This meta-analysis showed that IV-VC treatment did not affect disease severity compared with placebo treatment or usual care (odds ratio [OR], 0.70; 95% CI, 0.45 to 1.07; P = 0.10). In addition, no statistically significant difference in mortality was observed between patients who received IV-VC treatment and those who did not (OR, 0.64; 95% CI, 0.41 to 1.00; P = 0.05). Moreover, the adjusted meta-analysis revealed that the use of IV-VC did not influence disease severity (OR, 0.67; 95% CI, 0.34 to 1.31; P = 0.242) or mortality (OR, 1.02; 95% CI, 0.75 to 1.40; P = 0.877) in comparison with a control group. The results of this meta-analysis demonstrated that short-term IV-VC treatment did not reduce the risk of severity and mortality in patients with COVID-19.

Risk factors for mortality in hemodialysis patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: New evidence from studies on risk factors for mortality in hemodialysis (HD) patients with COVID-19 became available. We aimed to review the clinical risk factors for fatal outcomes in these patients. METHODS: We performed meta-analysis using the PubMed, EMBASE, and Cochrane databases. A fixed- or random-effects model was used for calculating heterogeneity. We used contour-enhanced funnel plot and Egger's tests to assess potential publication bias. RESULTS: Twenty-one studies were included. The proportion of males was lower in the survivor group than in the non-survivor group (OR = 0.75, 95% CI [0.61, 0.94]). The proportion of respiratory diseases was significantly lower in the survivor group than in the non-survivor group (OR = 0.42, 95% CI [0.29, 0.60]). The proportion of patients with fever, cough, and dyspnea was significantly lower in the survivor group (fever: OR = 0.53, 95% CI [0.31, 0.92]; cough: OR = 0.50, 95% CI [0.38, 0.65]; dyspnea: OR = 0.25, 95% CI [0.14, 0.47]) than in the non-survivor group. Compared with the non-survivor group, the survivor group had higher albumin and platelet levels and lower leucocyte counts. CONCLUSIONS: Male patients might have a higher risk of developing severe COVID-19. Comorbidities, such as respiratory diseases could also greatly influence the clinical prognosis of COVID-19. Clinical features, such as fever, dyspnea, cough, and abnormal platelet, leucocyte, and albumin levels, could imply eventual death. Our findings will help clinicians identify markers for the detection of high mortality risk in HD patients at an early stage of COVID-19.

The association between severe or death COVID-19 and solid organ transplantation: A systematic review and meta-analysis.

BACKGROUND: The effect of solid organ transplantation (SOT) on the severity and mortality of coronavirus disease 2019 (COVID-19) remained controversial. There is still no consensus on whether solid organ transplantation (SOT) recipients with COVID-19 are at greater risk of developing severe or fatal COVID-19. Therefore, we conducted a systematic review and meta-analysis to investigate the association between SOT, severe COVID-19 illness, and mortality. METHODS: A systemically comprehensive search in Pubmed, Embase, the Cochrane Library, Web of Science, and China National Knowledge Infrastructure was performed for relevant studies and articles. Consequently, we pooled the odds ratio (OR) from individual studies and performed heterogeneity, quality assessment and subgroup/sensitivity analysis. RESULTS: A total number of 15 articles with 265,839 participants were included in this study. Among the total number of participants, 1485 were SOT recipients. The meta-analysis results showed that transplant patients with COVID-19 were remarkably associated with a higher risk of intensive care unit admission than non-transplant patients (OR = 1.57, 95%CI: 1.07 to 2.31, P = 0.02). On the other hand, there were no statistically significant differences between SOT recipients and non-SOT recipients in mechanical ventilation need (OR = 1.55, 95%CI: 0.98 to 2.44, P = 0.06). In addition, we found that SOT recipients with COVID-19 had 1.40-fold increased odds of mortality than non-SOT recipients (OR = 1.40, 95%CI: 1.10 to 1.79, P = 0.007). Moreover, pooled analysis of adjusted results revealed that SOT recipients had a greater risk of mortality compared with non-SOT patients (HR = 1.54, 95%CI: 1.03 to 2.32, P = 0.037). LIMITATIONS: The main limitations in our study are attributed to the relatively small sample size, short follow-up period, and the fact that most of the studies included were retrospective in design. CONCLUSIONS: The results of this study indicate that SOT recipients with COVID-19 had a more significant risk of COVID-19 severity and mortality than the general population.

Effect of antiplatelet treatments on patients with COVID-19 infection: A systematic review and meta-analysis.

Despite the rationale that early anti-platelet would lower the risk of major organ dysfunction, the effectiveness of this approach remains controversial. Therefore, we perform a systematic review and meta-analysis to investigate the effect of antiplatelet treatments on patients with COVID-19 infection. An electronic search was carried out in Pubmed, Embase, Cochrane library, Web of Science, MEDLINE, Wanfang and China National Knowledge Infrastructure (CNKI). Meta-analysis and statistical analyses were completed with using the RevMan 5.3 and Stata 12.0. A total of 9 articles representing data from 5970 participants were included in this study. The meta-analysis showed antiplatelet agents were not associated with higher risk of severe COVID-19 disease (OR = 0.98, 95%CI: 0.64 to 1.50, P = 0.94; I 2 = 65%), while an adjusted analysis indicated that antiplatelet agents was not associated with an increased risk of mortality (OR = 0.65, 95%CI: 0.40 to 1.06, P = 0.498; I 2 = 0%). The results of this study reveal that while there is no significant benefit on mortality demonstrated with the use of antiplatelet agents, the upper bound of the confidence interval suggests that there is unlikely to be a compelling risk of harm associated with this practice. The benefit and risk of the use of antiplatelet agents should be fully considered especially in the presence of thrombocytopenia status in patients with COVID-19.

Association of neutrophil-to-lymphocyte ratio and risk of cardiovascular or all-cause mortality in chronic kidney disease: a meta-analysis.

BACKGROUND: It is currently controversial whether neutrophil-to-lymphocyte ratio (NLR) has a prognostic role in patients with chronic kidney disease (CKD). We aimed to investigate whether NLR was an independent predictor of cardiovascular or all-cause mortality in CKD patients with or without hemodialysis by performing a meta-analysis. METHODS: Pubmed, Embase, and Cochrane Library databases are systematically searched for relevant literature that investigated NLR and subsequent cardiovascular or all-cause mortality risk in CKD with or without dialysis. Pooled hazard risk (HR) with 95% confidence interval (CI) was calculated for the high vs. low NLR category. RESULTS: A total of thirteen studies enrolling 116,709 patients were identified and analyzed. In summary, high NLR was associated with an increased risk of all-cause mortality (HR 1.93, 95% CI 1.87-2.00; P < 0.00001) and cardiovascular mortality (HR 1.45, 95% CI 1.18-1.79, P < 0.001). Subgroup analysis indicated that high NLR are independently associated with all-cause mortality risk in dialysis patients (HR 1.94, 95% CI 1.87-2.01; P < 0.00001). CONCLUSIONS: This meta-analysis indicates a high NLR is related to all-cause mortality and cardiovascular mortality in patients with chronic kidney disease. Dialysis patients with high NLR are candidates at high risk of mortality to allow for earlier interventions. Further large scale and more rigorously designed studies are warranted to confirm the prognostic value of NLR in the different stages of CKD.